Abrams Charles K
Department of Neurology and Rehabilitation, University of Illinois at Chicago College of Medicine, Chicago, Illinois
disorders are typically characterized by peripheral motor and sensory neuropathy with or without fixed CNS abnormalities and/or acute, self-limited episodes of transient neurologic dysfunction (especially weakness and dysarthria). Peripheral neuropathy typically manifests in affected males between ages five and 25 years. Although both men and women are affected, manifestations tend to be less severe in women, some of whom may remain asymptomatic. Less commonly, initial manifestations in some affected individuals are stroke-like episodes (acute fulminant episodes of reversible CNS dysfunction).
DIAGNOSIS/TESTING: The diagnosis of CMT1X is established in a male by identification of a hemizygous pathogenic variant on molecular genetic testing and in a female by identification of a heterozygous pathogenic variant.
Treatment by a multidisciplinary team includes special shoes and/or ankle/foot orthoses to correct foot drop and to aid walking; surgery as needed for severe ; forearm crutches, canes, wheelchairs as needed for mobility; daily heel cord stretching to prevent Achilles' tendon shortening; exercise as tolerated. Treatment of stroke-like episodes is supportive, as these are self-limited. Yearly examinations by: a neurologist of motor function and pain; a physical therapist of gross motor skills and activities of daily living (ADL), an occupational therapist of fine motor skills and ADL; a foot care specialist for pressure sores and/or poorly fitting footwear. More frequent self-foot examination by the affected individual. Obesity (makes ambulation more difficult); medications that are toxic or potentially toxic to persons with CMT.
CMT1X is inherited in an X-linked manner. Affected males transmit the pathogenic variant to all of their daughters and none of their sons. Women with a pathogenic variant have a 50% chance of transmitting the pathogenic variant to each child. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygotes and may have mild-to-no manifestations or, more often, mild-to-moderate manifestations that may progress. Once the pathogenic variant has been identified in an affected family member, molecular genetic testing of at-risk female relatives to determine their genetic status, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.
这些疾病通常的特点是伴有或不伴有固定的中枢神经系统异常和/或急性、自限性的短暂神经功能障碍发作（尤其是肌无力和构音障碍）的周围运动和感觉神经病变。周围神经病变通常在5至25岁的男性患者中出现。虽然男性和女性都会受到影响，但女性的症状往往较轻，其中一些人可能没有症状。较少见的情况是，一些患者的初始表现为类似中风的发作（可逆性中枢神经系统功能障碍的急性暴发性发作）。
诊断/检测：通过分子基因检测鉴定出半合子致病变异可确诊男性CMT1X，鉴定出杂合子致病变异可确诊女性CMT1X。
多学科团队的治疗包括特殊鞋子和/或踝足矫形器以纠正足下垂并辅助行走；根据需要进行严重情况下的手术；根据需要使用前臂拐杖、手杖、轮椅以辅助行动；每天进行跟腱拉伸以防止跟腱缩短；根据耐受情况进行锻炼。对类似中风发作的治疗是支持性的，因为这些发作是自限性的。每年由以下人员进行检查：神经科医生检查运动功能和疼痛情况；物理治疗师检查粗大运动技能和日常生活活动能力（ADL）；职业治疗师检查精细运动技能和ADL；足部护理专家检查压疮和/或不合脚的鞋类情况。患者需更频繁地自行检查足部。肥胖（使行走更加困难）；对CMT患者有毒或潜在有毒的药物。
CMT1X以X连锁方式遗传。患病男性会将致病变异传递给所有女儿，而不会传递给任何儿子。携带致病变异的女性将致病变异传递给每个孩子的概率为50%。继承致病变异的男性会患病；继承致病变异的女性将成为杂合子，可能有轻度至无表现，或者更常见的是有轻度至中度表现，且这些表现可能会进展。一旦在患病家庭成员中鉴定出致病变异，就可以对有风险的女性亲属进行分子基因检测以确定她们的基因状态，对高风险妊娠进行产前检测，以及进行植入前基因检测。
